• 대한생식의학회:학술대회논문집
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• 2000.02a
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• pp.21-30
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• 2000

• Clinical and Experimental Reproductive Medicine
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• v.45 no.3
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• pp.135-142
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• 2018

Objective: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods: Randomized patients in all three groups (early antagonist, n = 14; conventional antagonist, n = 11; long agonist, n = 11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. Results: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p= 0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p= 0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p= 0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p= 0.324). Conclusion: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.4
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• pp.228-233
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• 2011

Objective: To investigate the effectiveness of GnRH antagonist multiple-dose protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment and GnRH agonist low-dose long protocol (LP). Methods: A total of 120 poor responders were randomized into three groups according to controlled ovarian stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1), GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low-dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were pretreated with OCP for 21days in the cycle preceding COS, and ovarian stimulation using recombinant human FSH (rhFSH) was started 5 days after discontinuation of OCP. Results: There were no differences in patients' characteristics among three groups. Total dose and days of rhFSH used for COS were significantly higher in group 3 than in group 1 or 2. The numbers of mature oocytes, fertilized oocytes and grade I, II embryos were significantly lower in group 2 than in group 1 or 3. There were no significant differences in the clinical pregnancy rate and implantation rate among three groups. Conclusion: GnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH agonist low-dose LP in poor responders and can benefit the poor responders by reducing the amount and duration of FSH required for follicular maturation.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.3
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• pp.261-268
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• 2005

Objective: To compare the clinical results and pregnancy outcomes of in vitro fertilization (IVF) between GnRH antagonist cycles and GnRH agonist (GnRH-a) cycles including flare-up and long protocol in women with advanced age. Materials and Methods: Retrospective clinical study. From January 2001 to September 2003, IVF cycles of female patient 37 years over were included in this study. GnRH-a long protocol (62 cycles, 61 patients) and GnRH antagonist multi-dose flexible protocol (66 cycles, 51 patients) were compared with the control group of GnRH-a flare-up protocol (151 cycles, 138 patients). IVF cycles for non-obstructive azoospermia (NOA), endometriosis III, IV and polycystic ovarian syndrome (PCOS) were excluded in this study. Clinical results such as total gonadotropin dose, serum E2 on hCG administration, the number of retrieved oocytes and the pregnancy outcomes - clinical pregnancy rate (CPR), implantation rate (IR) and live birth rate (LBR) per embryo transfer - were compared. Results: There were significant differences in the total dose of gonadotropin (GnRH-a flare-up vs. GnRH-a long vs. GnRH-antagonist; 41.8 vs. 54.7 vs. 24.8), serum E2 on hCG administration (1787.2 vs. 1881.6 vs. 788.0), the numbers of retrieved oocytes (8.1 vs. 11.1 vs. 4.5) and endometrial thickness (9.1 vs. 10.4 vs. 8.0) which were significantly lower in GnRH-antagonist cycles. But pregnancy outcomes shows no significant differenced in CPR (25.0% vs. 35.8% vs. 24.5%), IR (11.7% vs. 12.3% vs. 10.1%) and LBR (15.8% vs. 28.3% vs. 15.1%) Conclusion: In women with advanced age, GnRH-antagonist cycles can result in comparable pregnancy outcomes to GnRH-a cycles including flare-up and long protocol. GnRH-a long protocol show higher CPR, IR and LBR than GnRH antagonist multi-dose flexible protocol and flare-up protocol without significant differences.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.4
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• pp.158-164
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• 2014

Objective: To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). Methods: A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. Results: The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). Conclusion: The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.

• 대한생식의학회:학술대회논문집
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• 2002.05a
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• pp.65-66
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• 2002

• 대한생식의학회:학술대회논문집
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• 2003.12a
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• pp.100-101
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• 2003

• Clinical and Experimental Reproductive Medicine
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• v.43 no.3
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• pp.169-173
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• 2016

Objective: To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozenthawed embryo transfer (FET) cycles following GnRH agonist treatment. Methods: This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. Results: GnRH agonist pretreatment increased the stimulation duration ($11.5{\pm}2.1days$ vs. $9.9{\pm}2.0days$) and total dose of gonadotropin ($3,421{\pm}1,141IU$ vs. $2,588{\pm}1,192IU$), which resulted in a significantly higher number of retrieved oocytes ($10.0{\pm}8.2$ vs. $7.9{\pm}6.8$, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes ($14.3{\pm}9.2$ vs. $10.0{\pm}8.2$, p=0.022) with a lower dose of gonadotropin ($2,974{\pm}1,112IU$ vs. $3,421{\pm}1,141IU$, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. Conclusion: FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further largescale prospective studies are required to confirm this result.

• Clinical and Experimental Reproductive Medicine
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• v.34 no.1
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• pp.49-56
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• 2007

Objective: To evaluate the effect of short coasting, by withdrawing both gonadotropins and GnRH agonist (GnRHa), on the prevention in severe ovarian hyperstimulation syndrome(OHSS) without compromising pregnancy outcome. Method: Thirty-seven women who had been coasted during COH for IVF were coasted when $\geq$20 follicles > 15 mm with serum E$_2$ level of 4,000 pg/ml were detected. Coasting was initiated for one or two days depending on the status of follicle on ultrasound and serum E$_2$ level. Both gonadotropin and GnRHa were withheld for coasting. Retrospective study was carried and changes of serum E$_2$ levels, number of oocytes retrieved, fertilization rate, pregnancy rate were compared and analyzed. Results: The mean serum E$_2$ level fell from 6,993 pg/ml on the onset of coasting to 3,396 pg/ml on the day of hCG administration. The mean number of oocytes retrieved and fertilization rate were 15.7 and 70.0%, respectively. Fifteen patients were pregnant (40.6%) and implantation rate was 15.2%. Twenty-six (70.3%) patients were coasted for one day and 11 (29.7%) were coasted for two days. The mean decrease rate of serum E$_2$ level was 43% in one day coasting group and 15% (1$^{st}$ day) and 81% (2$^{nd}$ day) in two day coasting group. The pregnancy outcome was similar between the two groups. After coasting, no severe or moderate OHSS occurred in any patients and mild OHSS occurred in 3(8.1%) patients. Conclusions: Coasting for one or two days can be used successfully in the prevention of OHSS without compromising IVF cycle outcome.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.55-65
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• 1999

There have been many reports to date regarding the role of GnRH as a local regulatory factor of ovarian function as studies of human and rat ovaries revealed GnRH and its receptor. In recent studies it has been shown that GnRH directly causes apoptosis in the granulosa cells of the rat ovary, and such results leads to the suggestion that the use of GnRH agonist for more stable long term ovarian hyperstimulation in human IVF-ET programs causes granulosa cell apoptosis which may lead to follicular atresia. Therefore this study attempts to determine if granulosa-luteal cell apoptosis occurs in patients during IVF-ET programs in which GnRH agonist is employed for ovarian hyperstimulation. The quality of oocyte-cumulus complexes obtained during ovum pickup procedures were assessed morphologically and then the fertilization rate and developmental rate was determined. Apoptotic cells among the granulosa-luteal cells obtained during the same procedure were observed after staining with Hematoxylin-eosin. The fragmentation degree of DNA extracted from granulosa-luteal cells was determined and comparatively analyzed. There was no difference in the average age of the patients, the number of oocytes retrieved, and fertilization and developmental rates between the FSH/hMG group and GnRH-long group. There was also no difference in the apoptosis rate and pyknosis rate in the granulosa-luteal cells between the two groups. However, when the oocyte-cumulus complexes were morphoogically divided into the healthy group and atretic group without regard for the method of hyperstimulation, the results showed that the number of oocytes obtained averaged $11.09{\pm}8.75\;and\;10.33{\pm}4.53$ per cycle, respectively, showing no significant difference, but the fertilization rate (77.05%, 56.99%, respectively, p<0.01) and developmental rate (65.96%, 41.51%, respectively, p<0.01) was significantly increased in the healthy group when compared to the atretic group. The degree of apoptosis in the granulosa-luteal cells showed that in the healthy group it was 2.25% which was not significantly different from the atretic group (2.77%), but the pyknosis rate in the atretic group (27.81%) was significantly higher compared to the healthy group (11.35%, p<0.01). The quantity of DNA fragmentation in the FSH/hMG group was 32.22%, while in the GnRH-long group it was 34.27%, showing no significant difference. On the other hand the degree of DNA fragmentation was 39.05% and 11.83% in the healthy group and atretic group, respectively, showing significantly higher increase in the atretic group (p<0.01). The above results suggest that death of granulosa-luteal cells according to the state of the oocyte-cumulus complex is more related to pyknosis rather than apoptosis. Also, the GnRH agonist used in ovarian hyperstimulation does not seem to directly affect the apoptosis of retrieved oocytes and granulosa-luteal cells, and which is thought to be due to the suppression of the apoptogenic effect of GnRH agonist as a result of the high doses of FSH administered.